B3847 - Allostatic load in childhood and the development of mental health disorders - 26/08/2021

B number: 
Principal applicant name: 
Zoltan Sarnyai | James Cook University (Australia)
Sabine Finlay
Title of project: 
Allostatic load in childhood and the development of mental health disorders
Proposal summary: 

The increased wear and tear on the body, is the consequence of multisystem regulations in response to repeated challenges from the environment (McEwen & Stellar, 1993). This multisystem dysregulation can be objectively quantified by calculating the allostatic load index, a cumulative score of biological biomarkers in the cardiovascular, immune, neuroendocrine, and metabolic systems (Berger et al., 2018; McEwen, 2004). Elevated allostatic load has been shown to predict the risk of major health outcomes, both systemically and in the brain. Evidence suggests that the elevation of individual biomarkers can be observed in early childhood (9 years old) in people who later develop a mental health disorder, however only a few biomarkers (IL-6 and CRP) has been investigated (Khandaker et al., 2014).
We and others have shown that severe mental disorder, such as schizophrenia, bipolar disorder and psychosis is associated with increased allostatic load (Berger et al., 2018; Berger et al., 2020; Juster et al., 2018; Piotrowski et al., 2019). Furthermore, our group has established that elevated allostatic load predicts depression symptoms and may underlie higher mental health burden and shortened life expectancy of a population affected by considerable stress and trauma, the Indigenous Australian people (Berger et al., 2019; Ketheesan et al., 2020)
This project will expand on these earlier findings and include biological markers from the four major physiological systems to calculate the allostatic load index and identify whether there is an association between a multisystem dysregulation in childhood and the development of severe mental health disorders. If such association is detectable, that will raise the possibility that the allostatic load index could be applied for targeting interventions in populations at risk and aiming to reduce the risk of developing a mental health disorder in adulthood.

Berger, M., Juster, R. P., Westphal, S., Amminger, G. P., Bogerts, B., Schiltz, K., Bahn, S., Steiner, J., & Sarnyai, Z. (2018). Allostatic load is associated with psychotic symptoms and decreases with antipsychotic treatment in patients with schizophrenia and first-episode psychosis. Psychoneuroendocrinology, 90, 35-42. https://doi.org/https://dx.doi.org/10.1016/j.psyneuen.2018.02.001
Berger, M., Lavoie, S., McGorry, P. D., Nelson, B., Markulev, C., Yuen, H. P., Schaefer, M., Sarnyai, Z., & Amminger, G. P. (2020). Relationship between allostatic load and clinical outcomes in youth at ultra-high risk for psychosis in the NEURAPRO study. Schizophrenia Research, 226, 38-43. https://doi.org/https://doi.org/10.1016/j.schres.2018.10.002
Berger, M., Taylor, S., Harriss, L., Campbell, S., Thompson, F., Jones, S., Sushames, A., Amminger, G. P., Sarnyai, Z., & McDermott, R. (2019). Hair cortisol, allostatic load, and depressive symptoms in Australian Aboriginal and Torres Strait Islander people [Research Support, Non-U.S. Gov't]. Stress, 22(3), 312-320. https://doi.org/https://dx.doi.org/10.1080/10253890.2019.1572745
Juster, R.-P., Sasseville, M., Giguère, C.-É., Consortium, S., & Lupien, S. J. (2018). Elevated allostatic load in individuals presenting at psychiatric emergency services. Journal of Psychosomatic Research, 115, 101-109. https://doi.org/10.1016/j.jpsychores.2018.10.012
Ketheesan, S., Rinaudo, M., Berger, M., Wenitong, M., Juster, R. P., McEwen, B. S., & Sarnyai, Z. (2020). Stress, allostatic load and mental health in Indigenous Australians* [Review]. Stress, 23(5), 509-518. https://doi.org/http://dx.doi.org/10.1080/10253890.2020.1732346
Khandaker, G. M., Pearson, R. M., Zammit, S., Lewis, G., & Jones, P. B. (2014). Association of serum interleukin 6 and C-reactive protein in childhood with depression and psychosis in young adult life: a population-based longitudinal study. JAMA Psychiatry, 71(10), 1121-1128. https://doi.org/https://dx.doi.org/10.1001/jamapsychiatry.2014.1332
McEwen, B. S. (2004). Protection and damage from acute and chronic stress: Allostasis and allostatic overload and relevance to the pathophysiology of psychiatric disorders. Annals of the New York Academy of Sciences, 1032, 1-7. https://doi.org/10.1196/annals.1314.001
McEwen, B. S., & Stellar, E. (1993). Stress and the individual. Mechanisms leading to disease. JAMA Internal Medicine, 1(18), 2093-2101.
Piotrowski, P., Kotowicz, K., Rymaszewska, J., Beszlej, J. A., Plichta, P., Samochowiec, J., Kalinowska, S., Trzesniowska-Drukala, B., & Misiak, B. (2019). Allostatic load index and its clinical correlates at various stages of psychosis. Schizophrenia Research, 210, 73-80. https://doi.org/https://dx.doi.org/10.1016/j.schres.2019.06.009

Impact of research: 
The concept of allostatic load, the multi-system disregulation in response to repeated toxic stress and trauma, is moving to the centre of investigating pathomechanisms and diagnistic/predictive biomarkers in psychiatry. There have been several convincing cross-sectional studies, including ours, to show elevated allostatic load in a variety of severe psychiatric disorders. However, there has been no study involving a longitudinal birth cohort conducted in this field. We expect that the unique power of the ALSPAC study will allow us to uncover that early childhood adversity results in a long-lasting multisystem dysregulation, measured as elevated allostatic load, which, in turn contribute to the development of psychiatric disorders in young adulthood. Furthermore, such relationship will indicate that the measurement of allostatic load may have predicitve power for the future emergence of mental illness in toxic stress/trauma exposed, vulnerable individuals, which can guide the development of novel interventions. The development of new algorhythms, rooted in an etiologically and mechanistically plausible framework (stress-trauma-mental illness), with preditive power, will have a significant practical impact in psychiatric diagnosis and treatment monitoring.
Date proposal received: 
Wednesday, 18 August, 2021
Date proposal approved: 
Thursday, 26 August, 2021
Mental health - Psychology, Psychiatry, Cognition, Mental health, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Childhood - childcare, childhood adversity, Hormones - cortisol, IGF, thyroid, Metabolic - metabolism